Nocebo effect in Dermatology

Abstract

Nocebo effect, originally denoting the negative counterpart of the placebo phenomenon, is now better defined as the occurrence of adverse effects to a therapeutic intervention because the patient expects them to develop. More commonly encountered in patients with a past negative experience, this effect stems from highly active processes in the central nervous system, mediated by specific neurotransmitters and modulated by psychological mechanisms such as expectation and conditioning. The magnitude of nocebo effect in clinical medicine is being increasingly appreciated and its relevance encompasses clinical trials as well as clinical practice. Although there is hardly any reference to the term nocebo in dermatology articles, the phenomenon is encountered routinely by dermatologists. Dermatology patients are more susceptible to nocebo responses owing to the psychological concern from visibility of skin lesions and the chronicity, unpredictable course, lack of 'permanent cure' and frequent relapses of skin disorders. While finasteride remains the prototypical drug that displays a prominent nocebo effect in dermatologic therapeutics, other drugs such as isotretinoin are also likely inducers. This peculiar phenomenon has recently been appreciated in the modulation of itch perception and in controlled drug provocation tests in patients with a history of adverse drug reactions. Considering the conflict between patients' right to information about treatment related adverse effects and the likelihood of nocebo effect stemming from information disclosure, the prospect of ethically minimizing nocebo effect remains daunting. In this article, we review the concept of nocebo effect, its postulated mechanism, relevance in clinical dermatology and techniques to prevent it from becoming a barrier to effective patient management.

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“…In addition, it is likely that there is a tendency to overestimate the incidence and severity of side effects in the information sheets of oral isotretinoin, as frequently happens with other drugs. 37 Teratogenicity This is the most important side effect. 38 Ingestion of oral isotretinoin in female patients of childbearing potential, independently of the dose, may induce major fetal malformations, premature birth, or spontaneous abortion in a high percentage of cases.…”

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“…Considering the occurrence and the complex etiology of PHL, it is widely accepted that new therapies have to be identified [ 11 ]. Moreover, FIN and MIN activity reaches a plateau within two years of usage and both produce adverse effects on patients [ 12 , 13 ].…”

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“…Side effects including decreased libido, impotence and gynecomastia are slightly higher with dutasteride than with FIN [36]. In addition, the nocebo effect, described for FIN [9] is also likely to be encountered with dutasteride in the more educated and internet-savvy patients. The long serum half-life of 4 weeks of dutasteride results in persistent suppression of DHT level even after dutasteride is ceased.…”

“…Indeed, there is now sufficient evidence supporting the role of factors other than hormones contributing significantly to the pathogenesis of AGA (vide infra). Thirdly, the sexual adverse effects (SAEs) of FIN, whether sustained actually or due to the nocebo effect [9], and the tediousness of twice-daily application of MNX often reduce patient compliance, necessitating the development of novel therapies. Lastly, despite the advantages of hair transplantation, many patients who are candidates for the same prefer to avoid undergoing a 'surgical' procedure for hair restoration.…”